Biomedical subjects

R Saral

Publications and source records attributed to R Saral.

At least 55 records · Page 3Linked to original sources

PubMed1989

Association of hepatic veno-occlusive disease with interstitial pneumonitis in bone marrow transplant recipients.

Hepatic veno-occlusive disease (HVOD) and interstitial pneumonitis (IP) are both widely regarded as toxicities of intensive cytoreductive therapy, but their association has not been previously examined. Risk factors for IP were evaluated in 154 patients given intensive cytoreductive therapy followed by allogeneic bone marrow transplantation during a 2 1/2 year period. IP occurred in 68 patients; HVOD occurred in 39. The actuarial incidence of IP in patients with VOD was 71% and 45% in those without VOD (p = 0.0002). In multivariate analysis, the diagnosis of hematologic malignancy (p less than 0.001), the occurrence of HVOD (p less than 0.01), and pretransplant CMV seropositivity (p less than 0.02) were significantly associated with IP. The individual relative risks for IP of presence to absence of these factors was 4.5 for the diagnosis of hematologic malignancy, 2.1 for HVOD, and 1.9 for CMV seropositivity. Pulmonary veno-occlusive disease (PVOD), a previously rare observation, was noted at autopsy in 1/5 (20%) patients with HVOD alone, 6/20 (30%) patients with IP alone, and 10/14 (71%) of patients with both HVOD and IP. The association of HVOD and IP is supportive of the concept that toxic effects of cytotoxic therapy have a major role in pathogenesis of HVOD and IP.

Anemia, Aplastic↗

PubMed1988

Management of mucocutaneous herpes simplex virus infections in immunocompromised patients.

Herpes simplex virus (HSV) infections are a significant cause of morbidity among immunocompromised patients, and in some instances these infections may be a primary cause of death. The overwhelming majority of these infections are caused by reactivation of the virus. The natural history of reactivated HSV infections in immunocompromised patients has been well described, and these infections occur predictably in particular patient populations. Antiviral therapy has been shown to be effective in treating or preventing HSV infections. Randomized, controlled, double-blind studies have demonstrated that acyclovir is the most effective compound currently available for treatment or prevention of HSV infections.

Acyclovir↗

PubMed1988

Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases.

PURPOSE: The syndrome of idiopathic hyperammonemia occurs in patients who have received high-dose cytoreductive therapy for the treatment of hematologic malignancy. It is characterized by abrupt alteration in mental status and respiratory alkalosis associated with markedly elevated plasma ammonium levels in the absence of any identifiable cause, and frequently results in intractable coma and death. Our goal was to survey clinical and pathologic manifestations of the disorder and discuss treatment options. PATIENTS AND METHODS: Plasma ammonium levels were measured in patients on the acute leukemia service or on the bone marrow transplant service at The Johns Hopkins Hospital, and a level more than twice normal was considered diagnostic of hyperammonemia. The syndrome was identified in nine patients; in eight, hyperammonemia occurred after administration of intensive cytoreductive therapy that resulted in profound leukopenia. The disorder occurred in the ninth patient two months after allogeneic bone marrow transplantation. RESULTS: Three of the nine patients survived an episode of idiopathic hyperammonemia; one patient subsequently died of leukemia and one of recurrent idiopathic hyperammonemia. The one long-term survivor is currently alive and well without neurologic sequelae 250 days after autologous bone marrow transplantation. CONCLUSION: Because neurologic function can deteriorate rapidly, early recognition of this disorder and close monitoring of the patient's neurologic status are critical.

Adolescent↗

PubMed1988

BK and JC virus infections in recipients of bone marrow transplants.

Fifty-five recipients of bone marrow transplants were monitored prospectively for urinary excretion of BK (BKV) and JC (JCV) viruses and for infections with other viruses. For both BKV and JCV, viruria occurred exclusively in patients who were seropositive at transplantation, a finding indicating that shedding of virus was very likely the result of reactivation. BKV reactivation, which occurred in 26 (55%) of 47 BKV-seropositive patients, was far more common than JCV reactivation, which was detected in only two (7%) of 30 JCV-seropositive patients (P less than .0001). In most patients, BK viruria began two to eight weeks after transplantation and resolved spontaneously after a two- to three-week period. Posttransplantation, there was a temporal pattern in the onsets of infection with the different viruses; herpes simplex virus infections occurred first (mean, 7 d), followed by BKV infections (mean, 33 d) and then cytomegalovirus infections (mean, 51 d). BK viruria was associated with hemorrhagic cystitis.

Antibodies, Viral↗

PubMed1988

Interstitial pneumonitis after allogeneic bone marrow transplantation. Nine-year experience at a single institution.

Of 386 patients with allogeneic bone marrow transplants (BMT) treated during a 9-year interval, 166 developed interstitial pneumonitis (IP). Idiopathic and cytomegalovirus (CMV) IP constituted 90% of the 113 cases in which tissue was examined. Risk factors for IP overall were acute graft-versus-host disease (AGVHD), remote transplant date, the diagnosis of leukemia, and GVHD prophylaxis with agents other than cyclosporine. Risk factors for CMV IP were pre-transplant CMV seropositivity, CMV excretion, age greater than 10 years, AGVHD, GVHD prophylaxis with agents other than cyclosporine, and a remote transplant date. Patients transplanted for aplastic anemia were at lower risk for idiopathic IP than those transplanted for leukemia. The incidence of IP in patients given busulfan plus cyclophosphamide was equivalent to that in patients receiving cyclophosphamide plus total body irradiation. The incidence of idiopathic IP remained constant over this 9-year period while CMV IP declined significantly.

Adult↗

PubMed1988

Interstitial pneumonitis following autologous bone marrow transplantation.

Interstitial pneumonitis (IP) occurred in 20 of 143 (14%) patients who received cytoreductive therapy followed by autologous bone marrow transplantation (BMT) as treatment for malignancy. IP occurred at a median onset time of 41 days (5 to 624 days). All but three of the episodes were fatal. Of the thirteen cases in which tissue was examined, half were idiopathic; the remainder were due to various infectious agents. The actuarial incidences of idiopathic (7%) and CMV IP (2%) in these marrow autograft recipients were lower than the incidences of idiopathic (19%) and CMV IP (17%) in comparably treated recipients of allogeneic BMT (P less than or equal to 0.001 for both comparisons).

Adolescent↗

PubMed1988

Successful marrow transplantation for acute myelocytic leukemia following therapy for Hodgkin's disease.

Five patients with acute myelocytic leukemia (AML) after combined modality therapy for Hodgkin's disease (HD) were treated with cyclophosphamide and busulfan followed by bone marrow transplantation (BMT). Four patients received allogeneic transplants from histocompatibility locus antigen (HLA)-compatible siblings and the fifth patient received an autologous marrow treated with 4-hydroperoxycyclophosphamide. Two patients died of complications of acute graft-v-host disease (GVHD) despite prophylaxis with either low-dose cyclophosphamide or cyclosporine. The remaining three patients were alive and disease-free 382, 617, and 620 days after transplant. These initial results are encouraging and more patients with treatment-related AML need to be evaluated with both allogeneic and autologous BMT to fully elucidate the potentially curative role of this intensive therapy in an otherwise fatal hematologic malignancy.

Adolescent↗

PubMed1988

Gastrointestinal inflammation after bone marrow transplantation: graft-versus-host disease or opportunistic infection?

Gastrointestinal inflammation after allogeneic bone marrow transplantation may be due to acute graft-versus-host disease (GVHD) and/or superinfection with opportunistic organisms. Twenty-eight patients with barium studies suggesting gastrointestinal inflammation after bone marrow transplantation and either acute GVHD, viral infection, or both were studied to characterize the radiographic appearances of each disease and to determine whether acute GVHD could be distinguished from viral superinfection on the basis of radiographic findings. Thirteen patients had minimal or no acute GVHD, with viral infection proved in eight and strongly suspected in four others; the remaining patient was thought to have nonspecific inflammatory bowel disease. Five patients had pure acute GVHD, and 10 patients had viral enteritis superimposed on acute GVHD. Radiographic abnormalities were found in the gastrointestinal tract in both acute GVHD and viral infection and were more extensive than previously reported. Findings were similar in both entities, although gastric abnormalities were not seen in pure acute GVHD but only in viral infection, either alone or together with acute GVHD. Prolonged small bowel barium coating occurred in both viral infection and acute GVHD. Fold thickening evolved into fold effacement with a shaggy contour in two patients with viral infection. Colonic findings in all groups mimicked ulcerative colitis. Our data indicate that differentiation between acute GVHD and viral enteritis is not possible on the basis of radiographic findings alone. Both entities should be considered when gastrointestinal inflammation occurs after bone marrow transplantation.

Adolescent↗

PubMed1988

Immunoglobulin E levels following allogeneic, autologous, and syngeneic bone marrow transplantation: an indirect association between hyperproduction and acute graft-v-host disease in allogeneic BMT.

Markedly elevated serum IgE levels have been noted following allogeneic bone marrow transplantation (BMT) and have been correlated with graft-v-host disease (GVHD) in several studies. To investigate this phenomenon, we measured serum IgE levels in 387 allogeneic, 143 autologous, and 21 syngeneic BMT recipients before and at intervals after BMT. As a population, allogeneic BMT recipients displayed a biphasic elevation in IgE levels, with peak levels occurring either early (days 15 to 19) or late (days 80 to 89) posttransplant. Only in individuals in whom peak levels occurred early did IgE level correlate with liver disease, histological changes, and overall clinical stage of GVHD. The association of IgE elevation and GVHD does not appear to be direct since recipients of syngeneic (monozygotic twin) grafts had the highest incidence of IgE hyperresponsiveness as well as the highest absolute IgE levels. Similarly, 22 recipients of autologous marrow not treated with 4-hydroperoxycyclophosphamide had elevated IgE levels comparable to those seen in allogeneic graft recipients. We hypothesize that augmented IgE synthesis and its subsequent resolution is the natural consequence of immune reconstitution in the presence of potentially reaginic agents such as antibiotics and infectious agents. As such, IgE hyperresponsiveness in syngeneic graft recipients may reflect the maturational sequence of IgE regulatory elements in the absence of interference by GVHD, GVHD therapy, or minor histocompatibility disparities. The cell populations required for IgE response (T cells, B cells, and antigen-presenting cells) may be reconstituted in advance of the regulatory elements that limit IgE production in healthy subjects. Although this temporal relationship does not appear to hold in allogeneic BMT, the balance between positive and negative factors, which determines the rates of IgE synthesis and catabolism, may be altered by GVHD, infection, and liver dysfunction acting alone or in combination.

Alanine Transaminase↗

PubMed1988

Bronchiolitis obliterans in bone marrow transplantation and its relationship to chronic graft-v-host disease and low serum IgG.

The records of 549 bone marrow transplant (BMT) patients at The Johns Hopkins Oncology Center during a 9-year period were reviewed to determine the incidence of bronchiolitis obliterans (BrOb). Seven patients had BrOb. All seven died, and BrOb was a contributing cause of death in six patients. Only recipients of allogeneic BMT were at risk for developing BrOb (2% incidence). Three cases were incidentally discovered at autopsy in patients who died less than 120 days after BMT from ventilatory failure owing to interstitial pneumonitis. Four cases were patients who died greater than 120 days after BMT. Of this latter group, all had overt chronic graft-v-host disease (CGVHD). Among 120 day survivors of allogeneic BMT, 6% of those with CGVHD developed BrOb as compared with none of those without CGVHD (P = .008). Five percent of patients with reduced IgG levels at day 120 developed BrOb as compared with none of those with normal IgG (P = .04). The incidence of BrOb in 120-day survivors was 14% (4 of 29) in patients with both CGVHD and decreased serum IgG, whereas patients with CGVHD only (0 of 25), those with decreased IgG levels only (0 of 53), and those with no CGVHD and normal IgG levels (0 of 70) did not develop BrOb.

Adolescent↗

PubMed1988

Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: results of a phase I clinical trial.

We report here the results of a phase I clinical trial using counterflow centrifugal elutriation (CCE) for the removal of donor T lymphocytes before allogeneic bone marrow transplantation (BMT). Thirty-eight patients received lymphocyte-depleted allografts from HLA-identical, MLR-nonreactive sibling donors. The patients entered onto the study were either at high risk on the basis of age (median, 39 years) or disease status (acute leukemia in early relapse [ER], chronic myelogenous leukemia [CML] in accelerated phase [AP], or therapy resistant [RES] lymphoma). All patients received a standard lymphocyte dose of 1 x 10(6) morphologic lymphocytes per kilogram ideal body weight (BW) and were maintained on cyclosporine A (CsA) for 170 days after BMT. Prompt engraftment occurred in 37 of 38 patients with a median time to absolute neutrophil count (ANC) greater than 500/microL of 18 days. Although acute graft-v-host disease (GVHD; clinical stage I or greater) was observed in 45%, it was limited to the skin in all but five patients. Survival was related to disease status at the time of BMT. Among patients with acute leukemia in first or second remission, CML in chronic phase (CP) or lymphoma in partial remission (PR), 64% are currently alive, in contrast to 31% of patients with acute leukemia in third remission or early relapse, CML in second CP or AP, or RES lymphoma. Median follow-up for all patients was 351 days (range, 105 to 711 days). We conclude that this procedure is safe and warrants further evaluation in a randomized efficacy trial.

Acute Disease↗

PubMed1988

Hypertension and renal dysfunction in bone marrow transplant recipients.

The incidence of acute renal failure, hypertension and electrolyte disorders in 64 bone marrow transplant recipients randomized to receive either cyclosporin or cyclophosphamide was investigated. Sixty-four per cent of patients developed acute renal failure, 75 per cent hypertension, and 88 per cent significant hypomagnesemia. The incidence of diastolic hypertension and hypomagnesemia was greater in the patents treated with cyclosporin. Hypomagnesemia was due to magnesium wasting by the kidney. Both groups received similar cumulative doses of aminoglycoside antibiotics. Significant proteinuria developed in all but one patient and nephrotic-range proteinuria was noted in 21 per cent. The cause of the proteinuria is unclear; no obvious morphologic changes were seen at autopsy in patients who exhibited nephrotic-range proteinuria. The abnormalities of renal function were shown to be transient in patients who were observed for periods ranging from one to three years. It is concluded that hypertension, renal failure and hypomagnesemia are common in the setting of bone marrow transplantation. Whereas cyclosporin probably aggravates the severity of these disorders, it is likely that other factors (e.g., aminoglycoside antibiotics) play a major role as shown by the high incidence of renal and electrolyte disorders in patients treated with cyclophosphamide alone.

Acute Kidney Injury↗

PubMed1987

Differences between first and subsequent fevers during prolonged neutropenia.

Fever during neutropenia before engraftment was studied in 86 consecutively treated patients undergoing allogeneic bone marrow transplantation. Eighty-four of the 86 patients experienced 132 febrile episodes. Only 26% of the patients had one fever which resolved with antibiotics. The rest required modification of antimicrobial therapy because of refractory fever (32%) or recurrent fevers (42%). The 121 fevers which occurred during neutropenia were analyzed to determine differences between first and subsequent fevers (79 and 42 episodes, respectively). The frequency of sepsis (23%) and defervescence (64%) did not differ between first and subsequent fevers. Presumed localized infection (PLI) was identified in 75% of first fever but in only 28% of subsequent fevers (P = 0.000002). Of the PLI identified, oropharyngeal mucosal disease accounted for 68% during first fever but only 38% during subsequent fevers (P = 0.02). Although sepsis in first fever was more frequently associated with PLI than sepsis in subsequent fevers (61% versus 10%, P = 0.01), overall, patients with PLI had a lower frequency of sepsis than those without (17% versus 32%, P = 0.04). Gram-negative pathogens were uniformly gentamicin sensitive in sepsis during first fever but were mostly gentamicin-resistant in sepsis during subsequent fevers (P = 0.01).

Adolescent↗

PubMed1987

BK virus specific humoral and cell mediated immunity in allogeneic bone marrow transplant (BMT) recipients.

BKV specific humoral and cell mediated immunity was examined weekly in 19 allogeneic BMT recipients and correlated with the occurrence of BKV shedding. Responses to staphylococcal antigen (SPL) and tetanus toxoid (TET) were measured as specificity controls. Responses and virus shedding were assayed weekly for up to 15 weeks after BMT. Fourteen of 19 patients enrolled in this study were immunized with TET on the day of transplant. Significant rises in TET specific IgG were observed in TET immunized, but not in unimmunized, subjects. Similarly, TET specific lymphoproliferative responses were observed only in TET immunized subjects when they emerged from aplasia 3 to 4 weeks later. In contrast, all subjects had positive lymphoproliferative responses to SPL, an antigen derived from a ubiquitous agent All subjects were assayed weekly for the presence of BKV in the urine as detected by ELISA. By 15 weeks, 11 (58%) of these patients shed detectable quantities of BKV antigen at least once. Subjects who excreted BKV (BKV+) maintained BKV specific IgG at pretransplant levels, whereas levels steadily declined in those who did not (BKV-) (p less than 0.001). Lymphoproliferative responses to BKV, TET, and SPL antigens were not significantly different across time or between excretion groups. The temporal relationship of BKV shedding and the expression of BKV specific immunity was investigated by examining average responses measured in 5-week intervals surrounding positive and negative antigen detection assays. Both BKV specific IgG and BKV specific lymphoproliferative responses were higher (1.8 fold, p less than 0.005 and 2.5 fold, p = 0.06, respectively) surrounding positive detection assays. These findings indicate a strong association between BKV excretion and the development of indicators of virus specific immunity following BMT.

Adolescent↗

PubMed1987

Allogeneic, syngeneic, and autologous bone marrow transplantation in the acute leukemias--Baltimore experience.

In presentation of our data in context of other clinical series, we have identified a few bone marrow transplant preparative regimens that appear to have a superior advantage over others as far as their antileukemic effects are concerned. So far, the delayed and late effects of the treatment appear to be quite acceptable considering the ultimate fatal outcome in the acute leukemias, in particular those in their second remission. GvHD and viral infections account for about two-thirds of the mortalities in series where leukemic relapse is very low. It is hoped that solutions or at least partial solutions will not only improve the overall therapeutic results, but will allow us to extend the procedure to older patients. It is suggested that the need for unrelated HLA "matched" donors may be supplanted by the use of autologous bone marrow transplants, particularly in the older patients.

Acute Disease↗

PubMed1987

Pneumatosis intestinalis in children after allogeneic bone marrow transplantation.

Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or high-grade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

Acute Disease↗

PubMed1987

Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole.

Patients treated with cytotoxic therapy expected to produce neutropenia lasting two or more weeks were randomly assigned in a double-blind study to receive intravenous miconazole or placebo concomitant with empiric antibiotics to test whether miconazole can prevent fungal sepsis. The study drug was initiated at the time of first fever along with antibiotics and was continued until neutropenia resolved, fungal sepsis occurred, or persistent or recurrent unexplained fever after six or more days prompted substitution of the study drug by amphotericin B. Two hundred eight treatment courses in 180 patients were evaluated. Fungal sepsis occurred in only one patient receiving miconazole compared with eight patients receiving placebo (p = 0.03). Fatal fungal sepsis occurred in four patients receiving placebo and in none of the patients receiving miconazole (p = 0.08). There was no evidence for the development of resistance to polyenes or imidazoles in fungal isolates recovered from patients in this randomized trial or an increase in Aspergillus infections in patients who received miconazole in this randomized trial or in 121 subsequently treated patients who received unblinded use of miconazole. Thus, intravenous miconazole was more effective than placebo in preventing fungal sepsis in patients with chemotherapy-induced prolonged neutropenia.

Adolescent↗

PubMed1987

Epithelial class II antigen expression in cutaneous graft-versus-host disease.

Induced class II histocompatibility antigens have been observed in the target tissues of rodents and humans with acute graft-versus-host disease (GVHD). Possibly this expression triggers the target tissue phase, through antigen presentation, lymphocyte recruitment, or additional antigenic stimulus. We have tested whether the induced expression is required for cutaneous GVHD in human marrow recipients. Ninety-two skin biopsies from 37 allogeneic marrow recipients at the Johns Hopkins Bone Marrow Transplant Unit were stained for HLA-DR, OKT6 (Langerhans cells), and for surface markers of lymphocyte and monocytes. Of 22 biopsies taken at the onset of GVHD, 12 did not have detectable HLA-DR antigen, and 10 had patchy-to-diffuse expression. The biopsies with HLA-DR- GVHD consisted primarily of epithelial infiltrates of cytotoxic/suppressor cells (CD8+), while those with HLA-DR+ GVHD had a mixed infiltrate with more helper/inducer/class-II-reactive cells (CD4+) in the epidermis and dermis and more monocytes in the dermis. Eight of 9 patients with HLA-DR- GVHD had follow-up biopsies that later expressed epithelial DR antigen, but the epidermal and dermal infiltrates showed no significant changes. Most of those receiving cyclosporine (CsA) prophylaxis (7/9) developed HLA-DR- GVHD, while those receiving cyclophosphamide were split between the two groups (8 of 13 were HLA-DR+). HLA-DR antigen expression was evident in some biopsies with no GVHD or minimal GVHD but did not appear to predict the development of GVHD or the type of GVHD. HLA-DR antigen expression was not evident in 2 of 3 initial biopsies of lichenoid-type chronic GVHD. Class II antigen induction is clearly not necessary for the target phase in most patients of this study.

Antigens, Surface↗